- Our aim was to evaluate safety and clinico-neurophysiological effects of repetitive Deep Transcranial Magnetic Stimulation (DTMS) in Parkinson’s Disease (PD), using the novel H-COIL. Fourteen PD-patients underwent 12 sessions 10 Hz-DTMS (4 weeks) over primary motor area opposite to their most affected side (W-M1) and prefrontal cortices. Clinical assessment (UPDRSIII; timed-tests including arm/foot tapping-AT/FT) and neurophysiological evaluation (Resting Motor Threshold-RMT, input–output curves-IO, Cortical Silent Period-CSP, intracortical inhibition-ICI/facilitation-ICF) were performed for worse (WS) and less affected (BS) sides. Patients were evaluated OFF therapy at baseline (T0) and before the last DTMS-session (T1). We found significant clinical improvements in UPDRSIII (41.9 ± 9.4 vs. 31.4 ± 7.9; p < 0.001), lateralized scores (p < 0.001 for both sides) and timed-test (p < 0.05 for AT and FT in both sides). Neurophysiological measures disclosed modifications in M1 excitability only in the worse hemisphere. RMT lowered from 36.5 ± 6.7 to 34.3 ± 6.4 (p = 0.04), MEP amplitude (120%RMT) increased (p = 0.04); ICI and ICF paralleled these modifications (3 and 15 ms; p = 0.05 and p = 0.04 respectively); CSP shortened (p = 0.05). No changes were observed for IO curves. Despite the lack of blindness, DTMS appears as a safe and promising new therapeutic perspective for non-invasive stimulation in PD. Neurophysiological changes on the worse side motor excitability paralleled clinical findings.